Phytomedicine最新文献

{"title":"Corrigendum to \"KAJF alleviated colorectal cancer liver metastasis by reshaping the gut microbiota and inhibiting M2-like macrophage polarization\" [Phytomedicine, 142(2025) 156766].","authors":"Zongmei Zheng, Yizhao Du, Hua Jiang, Zhenpeng Shi, Hailun Zhou, Lijing Jiao, Peifeng Liu, Yabin Gong","doi":"10.1016/j.phymed.2025.156848","DOIUrl":"10.1016/j.phymed.2025.156848","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156848"},"PeriodicalIF":6.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celastrol protected the MPTP-injected mice Parkinson's disease model via redox regulation of CDC37","authors":"Wanfen Liao ,&nbsp;Aiwen Dong ,&nbsp;Fatima Hafeez ,&nbsp;Qinyong Ye ,&nbsp;En Huang","doi":"10.1016/j.phymed.2025.157067","DOIUrl":"10.1016/j.phymed.2025.157067","url":null,"abstract":"<div><h3>Background</h3><div>Celastrol (CEL), a bioactive compound isolated from Tripterygium Wilfordii Hook. F, exerts neuroprotective effects through anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms in several neurodegenerative diseases, including Parkinson's disease (PD). CEL covalently binds to the thiol group of cysteine residues in cell division cycle 37 (CDC37), leading to redox-dependent modulation of CDC37 function. However, whether CEL redox regulates CDC37 and CEL-CDC37 interaction plays a role in pathogenesis of PD is still not be investigated yet. This study aids to demonstrate the role of CEL redox regulation of CDC37 in an MPTP-induced mouse model of PD.</div></div><div><h3>Methods</h3><div>Lentiviral vectors were used to overexpress or knock down CDC37 in MPTP-injected mice. CEL was administered to assess its effect on CDC37 redox status and related molecular pathways.</div></div><div><h3>Results</h3><div>CDC37 overexpression alleviated MPTP-induced motor deficits and dopaminergic neuron loss, whereas CDC37 knockdown exacerbated these impairments. Overexpression of CDC37 also suppressed activation of the NF-κB pathway and reduced phosphorylation of α-synuclein at serine 129 (p-S129-syn). MPTP insult decreased the reduced (active) form of CDC37 due to oxidative stress. CEL treatment restored CDC37 redox status, improved locomotor performance, preserved dopaminergic neurons, and inhibited both NF-κB activation and p-S129-synuclein levels. These effects were mediated by CEL's redox regulation of CDC37, which prevented its overoxidation, disrupted the Hsp90/CDC37 complex, and suppressed downstream pro-inflammatory and pro-pathogenic signaling.</div></div><div><h3>Conclusion</h3><div>Our study suggests that CEL restores the protective role of CDC37 in the MPTP-injected Parkinson's disease (PD) mouse model via redox regulation of CDC37, which prevents over-oxidation of CDC37 under high oxidative stress, and disrupts the Hsp90/CDC37 complex and subsequently blocks NF-κB pathway activation and p-S129-synuclein production. This study might provide a promising strategy for PD and further understanding of the therapeutic mechanism of CEL application.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157067"},"PeriodicalIF":6.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blueberry anthocyanins ameliorate arsenic-induced cognitive impairment in rats: mitigating mitochondrial damage and dysregulation","authors":"Xinbo Ma ,&nbsp;Yang Liu ,&nbsp;Bo Ding ,&nbsp;Yanan Liu ,&nbsp;Yuchen Zhang ,&nbsp;Yuxi Wang ,&nbsp;Liu Yang ,&nbsp;Yanmei Yang ,&nbsp;Xiaona Liu","doi":"10.1016/j.phymed.2025.157062","DOIUrl":"10.1016/j.phymed.2025.157062","url":null,"abstract":"<div><h3>Background</h3><div>Blueberry anthocyanin extract (BAE) is a natural antioxidant flavonoid found in blueberries that has the potential to alleviate oxidative stress-induced neurodegeneration. Previous studies have demonstrated the potential of BAE to mitigate arsenic-induced cognitive impairment; however, the underlying protective mechanisms remain elusive.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the effectiveness of BAE in reducing arsenic-induced cognitive impairment and explored whether BAE's neuroprotective effects are related to its antioxidant and mitochondrial protective effects.</div></div><div><h3>Methods</h3><div>Sixty male rats were exposed to sodium arsenite (NaAsO₂, 10 mg/kg) with or without BAE (100 and 200 mg/kg) for 12 weeks. Spatial learning and memory were evaluated using the Morris water maze (MWM). Neuronal damage in rat hippocampi was evaluated using hematoxylin and eosin (H&amp;E) staining, electron microscopy, and terminal deoxynucleotidyl transferase-mediated nick-end labelling (TUNEL) staining. Oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) were measured. Mitochondrial function was assessed by analysing peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), deacetylase sirtuin 1 (SIRT1), and proteins related to mitochondrial biogenesis and mitochondrial dynamics.</div></div><div><h3>Results</h3><div>Arsenic exposure significantly impaired learning and memory in rats, as evidenced by reduced performance in the MWM, whereas BAE treatment ameliorated these deficits. Furthermore, BAE alleviated arsenic-induced hippocampal neuronal apoptosis, as well as alleviating increased oxidative stress, weakened antioxidant capacity, and imbalanced mitochondrial biogenesis and dynamics. In this study, we focused on the core of mitochondrial quality control mechanism - mitochondrial biogenesis, fusion and fission. We explored the protective mechanism of BAE against arsenic - induced nerve damage. Based on these, we proposed an innovative therapeutic strategy: using natural products to target and regulate mitochondrial quality control.</div></div><div><h3>Conclusion</h3><div>This study indicated that BAE alleviates arsenic-induced neurotoxicity through its antioxidant and mitochondrial protective effects, effectively reducing arsenic-induced neurotoxicity and enhancing cognitive function.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157062"},"PeriodicalIF":6.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptome and metabolome analysis reveals the therapeutic mechanism of Huang-Qi-Si-Wu-Tang in experimental pulmonary arterial hypertension","authors":"Ye Wang ,&nbsp;Zhuangjie Guo ,&nbsp;Xinqi Ma ,&nbsp;Qing Xu ,&nbsp;Dandan Li ,&nbsp;Jie Yang ,&nbsp;Xiaoxuan Lu ,&nbsp;Peiran Yang ,&nbsp;Hongchun Zhang ,&nbsp;Hongmei Zhao ,&nbsp;Chen Wang","doi":"10.1016/j.phymed.2025.157058","DOIUrl":"10.1016/j.phymed.2025.157058","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary arterial hypertension is a complex vascular disease involving pathological remodeling of vascular cells, inflammatory cells, and the extracellular matrix. Current PAH therapies, which are primarily vasodilators, cannot reverse the disease pathogenesis or cure PAH. Novel therapeutic agents targeting the core process of vascular remodeling are desperately needed, and their mechanisms warrant systematic investigation.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the therapeutic potential of Huang-Qi-Si-Wu-Tang (HQSWT), a traditional Chinese herbal formula, in experimental models of PAH and to elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>We used monocrotaline-induced PAH in rats as an experimental model. We assessed the effect of HQSWT on disease prevention, as well as its effect in mitigating established disease. We employed RNA sequencing, integrated metabolomics and transcriptomics analysis, and validated findings by multiplex immunohistochemistry and quantitative PCR.</div></div><div><h3>Results</h3><div>HQSWT dose-dependently prevented monocrotaline-induced PAH development and mitigated established PAH, right ventricular hypertrophy, and pulmonary vascular remodeling. Transcriptomic analysis revealed HQSWT’s action on extracellular matrix pathways, including <em>Fn1</em> and <em>Thbs2</em>. Furthermore, we observed modulation of arachidonic acid metabolism via the ALOX5-LTB₄ axis. HQSWT reduced ALOX5 expression in lung tissue and perivascular macrophages.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that HQSWT is effective in treating experimental PAH. Through omics analysis, we have identified a novel mechanism of action whereby HQSWT may exert its protective effects by simultaneously targeting the extracellular matrix and inflammation-mediated pulmonary vascular remodeling, suggesting its potential as a new therapy for PAH.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157058"},"PeriodicalIF":6.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fucoidan alleviates renal fibrosis in mice via Akkermansia muciniphila-mediated suppression of NEU1-TLR4-NFκB signaling axis","authors":"Zhen Wang ,&nbsp;Xiao-Ling Rong ,&nbsp;Cai-Xia Dai ,&nbsp;Qing Wang ,&nbsp;Lin-Feng Lu ,&nbsp;Wen-Tao Zhang ,&nbsp;Lei Zhang ,&nbsp;Qian-Qian Chen ,&nbsp;E-Hu Liu","doi":"10.1016/j.phymed.2025.157060","DOIUrl":"10.1016/j.phymed.2025.157060","url":null,"abstract":"<div><h3>Background</h3><div>Fucoidan, a bioactive sulfated polysaccharide, is renowned for its extensive range of biological activities, including anticancer activity, antioxidative properties, immune activation and has demonstrated supportive therapeutic effects in treating kidney ailments. However, the underlying mechanism related to renal fibrosis remains not fully understood.</div></div><div><h3>Purpose</h3><div>The aim of this study was to elucidate the protective effects and mechanism of FPS against renal fibrosis with a focus on gut-kidney axis.</div></div><div><h3>Methods</h3><div>We established renal fibrosis models in mice using unilateral ureteral obstruction (UUO), folic acid (FA) challenge, or a microbiota-depleted, with continuous oral administration of FPS, <em>Akkermansia muciniphila</em> (<em>AKK</em>), or acetate at specified doses and intervals. Simultaneously, we examined the impact of FPS on epithelial mesenchymal transformation in cultured HK-2 and investigated the associated mechanisms.</div></div><div><h3>Results</h3><div>In this study, we demonstrate that fucoidan administration reduces renal collagen deposition, inflammation, epithelial mesenchymal transformation and improves renal function in mouse models of renal fibrosis induced by UUO or FA. Metagenomics analysis showed that fucoidan significantly increases the abundance of <em>AKK</em> by promoting its growth in UUO-induced renal fibrosis. Oral administration of live <em>AKK</em> alleviates renal fibrosis in UUO and FA mouse models. Using oral antibiotic-treated mice, we found that the effect of fucoidan on renal fibrosis was weakened. Gas chromatography-mass spectrometry (GC–MS/MS) study results show that <em>AKK</em> produces the short-chain fatty acids (acetate), which protects against renal fibrosis by suppressing NEU1-TLR4-NFκB-mediated inflammation in the kidney.</div></div><div><h3>Conclusion</h3><div>Our findings establish a novel gut-kidney axis wherein fucoidan ameliorates renal fibrosis through <em>AKK</em>-mediated acetate production and subsequent NEU1-TLR4-NFκB pathway inhibition.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157060"},"PeriodicalIF":6.7,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oroxyloside inhibits liver fibrosis and hepatocarcinogenesis dependent on hepatocyte-specific knockout of Atg5","authors":"Yunyao Liu ,&nbsp;Liu Chen ,&nbsp;Xingyu Liu ,&nbsp;Ran Tao ,&nbsp;Ran Dong ,&nbsp;Xiaosheng Wang ,&nbsp;Jiangti Luo ,&nbsp;Hanhan Li ,&nbsp;Yufen Zheng ,&nbsp;Lei Qiang ,&nbsp;Zhenzhong Deng ,&nbsp;Xiaoping Wang","doi":"10.1016/j.phymed.2025.157053","DOIUrl":"10.1016/j.phymed.2025.157053","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><div>Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is closely linked to liver fibrosis, yet effective preventive therapies remain elusive. Autophagy is a critical cellular process that maintains hepatic homeostasis, and its disruption is implicated in the progression of fibrosis and HCC. This study aimed to evaluate the efficacy of oroxyloside (OAG), a flavonoid derived from <em>Scutellaria baicalensis</em>, in preventing liver fibrosis associated with cancer.</div></div><div><h3>Methods</h3><div>Mouse models of liver fibrosis and hepatocarcinogenesis were developed using carbon tetrachloride (CCl₄) alone or a combined with diethylnitrosamine (DEN), with or without OAG treatment. Hepatocyte-specific Atg5 knockout mice (<em>Atg5</em>^Hep-/−) and <em>In vitro</em> models with silenced Atg5 or PPARγ were used to investigate autophagy's role in OAG's therapeutic effects. To analyze the correlation between autophagy and hepatic fibrosis or cancer we use the TCGA and GSE database. Patient tissue samples (79 pairs) associated HCC was investigated by immunohistochemistry.</div></div><div><h3>Results</h3><div>This study demonstrates that OAG restores autophagic flux through the AMPK-ULK1 pathway in a PPARγ-dependent manner, reducing oxidative stress, DNA damage, and inflammatory cytokine IL-6 production. These mechanisms culminate in the inhibiting the activation of hepatic stellate cell activation and fibrosis progression. OAG also significantly attenuated liver tumor burden and improved survival in a chronic liver injury model. Importantly, the therapeutic effects of OAG were diminished in Atg5-deficient hepatocytes, highlighting its reliance on autophagy. This mechanistic insight differentiates OAG from existing anti-fibrotic or HCC therapies by targeting the interplay between autophagy and inflammation.</div></div><div><h3>Conclusion</h3><div>OAG represents an innovative therapeutic approach to liver fibrosis and HCC, acting through autophagy-dependent pathways to inhibit inflammation and oxidative stress. Its dual anti-fibrotic and anti-carcinogenic effects position OAG as a promising candidate for addressing the unmet clinical needs in chronic liver disease.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157053"},"PeriodicalIF":6.7,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breviscapine injection and its main component scutellarin prevents lethal enterovirus infection by inhibiting neuroinflammation and oxidative stress in newborn mice","authors":"Wenhui Yang ,&nbsp;Junyi Wang ,&nbsp;Yi Tao ,&nbsp;Xiaodi Li ,&nbsp;Shanbo Tao ,&nbsp;Huilin Zhu ,&nbsp;Xi Chen ,&nbsp;Jinjun Shan ,&nbsp;Yongming Li ,&nbsp;Tonghui Ma ,&nbsp;Peng Cao ,&nbsp;Guangyi Cui","doi":"10.1016/j.phymed.2025.157042","DOIUrl":"10.1016/j.phymed.2025.157042","url":null,"abstract":"<div><h3>Background</h3><div>Enterovirus 71 (EV71) is the primary cause of severe neurological infections associated with Hand, Foot and Mouth Disease (HFMD) in children, and no specific therapeutic agent is available. Breviscapine injection (BRE Injection) is widely used in China for its neuroprotective properties in ischemic stroke.</div></div><div><h3>Objective</h3><div>To investigate the therapeutic impact and mechanisms of BRE Injection and its main component scutellarin in preventing fatal infection of EV71 in newborn mice.</div></div><div><h3>Methods</h3><div>A fatal EV71 infection model in newborn mice was developed to evaluate the effectiveness of BRE Injection and its main component scutellarin. The antiviral effects were analyzed using EV71-infected cell culture models. Molecular biology and histochemistry techniques were used to explore the underlying mechanisms.</div></div><div><h3>Results</h3><div>BRE Injection and its principal component, scutellarin (SCU, ≥99 %), successfully safeguarded newborn mice against fatal EV71 infection. EV71 infection predominantly occurred in the peripheral regions of the brainstem in the brain, with astrocytes being the most commonly infected cell type, and microglia showing the highest infection rate. SCU demonstrated antiviral activity with EC₅₀ values between 4.11 and 6.62 μM across different glial cells types. It inhibits EV71 replication, mitigates oxidative stress, reduces neuroinflammation by modulating the Kelch-like ECH Associated Protein 1/Nuclear Factor erythroid 2-Related Factor 2 (Keap1/Nrf2) and RELA proto-oncogene, NF-kB subunit/NLR family pyrin domain containing 3 (P65/NLRP3) pathways.</div></div><div><h3>Conclusion</h3><div>SCU from BRE Injection safeguarded newborn mice against fatal EV71 infection by inhibiting viral replication, and reducing oxidative damage and neuroinflammation. The underlying mechanisms involve enhancement of Keap1/Nrf2 pathway and inhibition of P65/NLRP3 pathway in glial cells of the brainstem.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157042"},"PeriodicalIF":6.7,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrine targets β-catenin and blocks the formation of β-catenin/TCF7L2 complex to promote ferroptosis and inhibit metastasis in triple-negative breast cancer","authors":"Yazhou Sang ,&nbsp;Yue Hu ,&nbsp;Ruohan Liang ,&nbsp;Yueyue Zhang ,&nbsp;Hongyuan Du ,&nbsp;Huilan Zhang ,&nbsp;Juan Chen ,&nbsp;Yaqiong Zhang ,&nbsp;Xuan Cao","doi":"10.1016/j.phymed.2025.157044","DOIUrl":"10.1016/j.phymed.2025.157044","url":null,"abstract":"<div><h3>Background</h3><div>Triple-negative breast cancer (TNBC) is still incurable, exhibiting a high propensity for metastasis. Matrine has been confirmed to possess anti-tumor properties. Nevertheless, the precise mechanism by which matrine inhibits TNBC metastasis remains uncertain.</div></div><div><h3>Purpose</h3><div>This investigation aimed to explore whether matrine could disrupt TNBC metastasis.</div></div><div><h3>Methods</h3><div>The migratory capacity of TNBC cells was assessed via wound healing and transwell assays. Then, we evaluated whether matrine directly interacts with β-catenin (β-cat). Molecular docking combined with plasmid point mutation was employed to ascertain the specific amino acid binding sites of matrine and β-cat. Next, we evaluated the impact of matrine on the formation of β-cat/transcription factor 7 like 2 (TCF7L2) complex and whether matrine could induce ferroptosis (FPT) in TNBC. The mouse lung metastasis model was utilized to assess the potential of matrine in inhibiting TNBC metastasis.</div></div><div><h3>Results</h3><div>Our research proved that matrine could directly target β-cat and abrogate the interaction of β-cat and TCF7L2, thus inhibiting the Wnt/β-cat downstream signaling pathway. Furthermore, matrine weakened the regulatory effect of TCF7L2 on glutathione peroxidase 4 (GPX4) and enhanced FPT by hindering the formation of the β-cat/TCF7L2 transcription complex. In addition, matrine-induced FPT effectively suppressed epithelial-mesenchymal transition (EMT) in TNBC.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that matrine impedes the stimulation of the Wnt/β-cat pathway, has anti-metastatic effects on TNBC by triggering ferroptosis and inhibiting EMT.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157044"},"PeriodicalIF":6.7,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative analysis reveals mechanisms of Prunella vulgaris in thyroid cancer metastasis","authors":"Shifan Zeng ,&nbsp;Benjuan Liu ,&nbsp;Rui Ge ,&nbsp;Zhilong Yuan ,&nbsp;Yunyun Yang ,&nbsp;Weiqiang Zhu ,&nbsp;Zhuo Wang","doi":"10.1016/j.phymed.2025.157051","DOIUrl":"10.1016/j.phymed.2025.157051","url":null,"abstract":"<div><h3>Background</h3><div>Lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is a major contributor to poor prognosis. Prunella vulgaris (P. vulgaris), a traditional medicinal herb, has shown potential in inhibiting PTC metastasis, but its molecular mechanism remains unclear.</div></div><div><h3>Objectives</h3><div>This study aimed to elucidate the molecular mechanisms by which <em>P. vulgaris</em> exerts its anti-metastatic effects on PTC, focusing on identifying key active compounds and their target genes.</div></div><div><h3>Methods</h3><div>RNA sequencing was used to identify differentially expressed genes (DEGs) between PTC and LNM tissues. Active compounds and targets of P. vulgaris were obtained from TCMSP and BATMAN-TCM and integrated with DEGs to construct a compound-target network. Machine-learning algorithms were applied to identify hub genes related to β-sitosterol (BS). The effects of BS and ADRB2 on cell viability, proliferation, migration, invasion, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were examined in vitro.</div></div><div><h3>Results</h3><div>696 DEGs and 195 P vulgaris targets were identified, with 91 overlapping genes intersecting DEGs and P. vulgaris targets. Within this network, 17 target genes were associated with BS, and five machine-learning algorithms consistently identified ADRB2 as a central hub. ADRB2 expression was significantly elevated in LNM tissues and closely correlated with clinicopathological features. BS treatment inhibited PTC cell growth and metastasis-related behaviors, which were reversed by ADRB2 overexpression.</div></div><div><h3>Conclusion</h3><div>BS, an active component of P. vulgaris, inhibits key processes associated with PTC metastasis by targeting ADRB2 and inducing mitochondrial dysfunction. These findings not only provide the first experimental evidence linking BS to ADRB2-mediated anti-metastatic activity in PTC, but also offer a novel integrated approach for identifying therapeutic compounds from traditional herbs.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157051"},"PeriodicalIF":6.7,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loganin epigenetically rescues mitochondrial complex III dysfunction via DNMT1-UQCRC1 demethylation to halt cardiac remodeling after myocardial infarction","authors":"Yunjing Wang ,&nbsp;Renshan Chen ,&nbsp;Huaqian Dou ,&nbsp;Junjun Huang ,&nbsp;Liyou Guo ,&nbsp;Liangyan Lu ,&nbsp;Anran Zheng ,&nbsp;Junhua Qi ,&nbsp;Peihua Li ,&nbsp;Jing Ling ,&nbsp;Xiaoling Zhang ,&nbsp;Xiuhui Chen ,&nbsp;Qing Xiao","doi":"10.1016/j.phymed.2025.157001","DOIUrl":"10.1016/j.phymed.2025.157001","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Loganin, an iridoid glycoside from Cornus officinalis, exhibits cardioprotective potential. While previous studies focused on its antioxidant and anti-inflammatory properties, its role in myocardial infarction (MI) remodeling remains unexplored. This study identifies the DNMT1-UQCRC1 methylation axis as a novel therapeutic target of Loganin, providing the first evidence of mitochondrial complex III regulation through DNA methylation in cardiac injury.</div></div><div><h3>Approach and results</h3><div>In a mouse model of MI, 7-day pretreatment with Loganin (15/30 mg/kg) markedly reduced infarct area, attenuated cardiac fibrosis, and improved functional recovery. RNA sequencing and functional analyses revealed Loganin restores mitochondrial complex III function by reversing MI-induced suppression of UQCRC1—a core subunit regulated through DNA hypermethylation. Loganin’s rescue of UQCRC1 expression and mitochondrial respiration depended on DNMT1, evidenced by reduced promoter methylation and restored complex III activity. Molecular docking and surface plasmon resonance confirmed Loganin directly binds DNMT1’s catalytic domain (KD = 13.5 μM), with in vitro assays showing DNMT1 enzymatic inhibition. Collectively, these results suggest Loganin addresses the epigenetic origin of mitochondrial failure to prevent post-MI remodeling.</div></div><div><h3>Conclusions</h3><div>Our study identifies Loganin as an epigenetic modulator that mitigates post-MI cardiac remodeling through DNMT1 inhibition, reversing methylation-dependent UQCRC1 repression to restore mitochondrial respiration. These findings define the DNMT1-UQCRC1 axis as an actionable therapeutic target for cardiac repair.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157001"},"PeriodicalIF":6.7,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}